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Nat Commun. 2018 Apr 3;9(1):1305. doi: 10.1038/s41467-018-03733-8.

Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment.

Author information

1
ETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, 4058, Basel, Switzerland.
2
Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
3
Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056, Basel, Switzerland.
4
Département Génie Biologique, Institut Universitaire de Technologie (IUTA), F-69622, Villeurbanne Cedex, France.
5
ETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, 4058, Basel, Switzerland. martin.fussenegger@bsse.ethz.ch.
6
Faculty of Life Science, University of Basel, Mattenstrasse 26, 4058, Basel, Switzerland. martin.fussenegger@bsse.ethz.ch.

Abstract

Exosomes are cell-derived nanovesicles (50-150 nm), which mediate intercellular communication, and are candidate therapeutic agents. However, inefficiency of exosomal message transfer, such as mRNA, and lack of methods to create designer exosomes have hampered their development into therapeutic interventions. Here, we report a set of EXOsomal transfer into cells (EXOtic) devices that enable efficient, customizable production of designer exosomes in engineered mammalian cells. These genetically encoded devices in exosome producer cells enhance exosome production, specific mRNA packaging, and delivery of the mRNA into the cytosol of target cells, enabling efficient cell-to-cell communication without the need to concentrate exosomes. Further, engineered producer cells implanted in living mice could consistently deliver cargo mRNA to the brain. Therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in in vitro and in vivo models of Parkinson's disease, indicating the potential usefulness of the EXOtic devices for RNA delivery-based therapeutic applications.

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PMID:
29610454
PMCID:
PMC5880805
DOI:
10.1038/s41467-018-03733-8
[Indexed for MEDLINE]
Free PMC Article

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